Previous results from our laboratory support the idea that the transcription factor CREB plays important roles as a mediator of neuroligands and growth factor signals in developing oligodendrocytes (OLGs). Moreover, we have recently observed that CREB phosphorylation is highly stimulated by the lipid bioactive molecule, sphingosine-1-phosphate (S1P). These results are crucial since they represent one of the first reports directly relating S1P with a transcription factor and could, therefore, allude to a novel mechanism of gene regulation in OLGs. Thus, in the proposed study we will focus on investigating (1) the developmental expression and identification of signaling pathways mediating the S1P-dependent stimulation of CREB phosphorylation, (2) the role of S1P in OLG development, and (3) the importance of S1P as a mediator of neurotrophin-3 actions in OLGs. A better understanding of the signaling pathways involved in OLG development will offer new avenues for the treatment of demyelinating conditions such as multiple sclerosis